The study is assembling a well-characterized cohort of patients with presumed chronic Lyme disease (or post treatment Lyme disease syndrome) and relevant controls. These patients are being extensively evaluated in a cross-sectional study and the patients with chronic Lyme disease will be followed prospectively. Patients who quelify will receive therapy with intravenous ceftriaxone. These studies will yield a prospective database upon which stringent diagnostic criteria can be established and future therapeutic trials can be designed. At this point, 116 patients and controls have been enrolled in the study. Multiple research projects are being developed based on the findings in this population. These include research in diagnostic tests, immunology and clinical manifestations. Examples of progress made in the past year include: Continuation of our collaboration with Dr. Mario Philipp and his group at Tulane University Medical Center in studying with a new diagnostic procedure for Lyme borreliosis, based on the C6 peptide of the VlsE protein. A manuscript describing the new findings has been accepted for publication at the Journal of Infectious Diseases. Continuation of our collaboration with Dr. Stephen Fischer from the Clinical Pathology Department at the Warren Grant Magnuson Clinical Center in the study of a new PCR assay for Borrelia. A study reporting the lack of evidence of B. burgdorferi infection in Alzheimer's disease, using this new PCR assay, has been published. (Marques A, Fahle G, Weir S, Fischer SH. Lack of evidence of Borrelia involvement in Alzheimer's disease. Journal of Infectious Diseases, 2000, 182: 1006-7.) Evaluation of a new culture media for B. burgdorferi, reported to be able to culture the spirochete from 43 out of 47 patients with chronic Lyme disease (Phillips, Infection 1998). When tested here, we were unable to culture the bacteria from 19 patients with CLD. Moreover, when we tried to grow the bacteria in this new media, it died after about 4-7 days. This study has been published. (Marques A, Stock F, Gill V. Evaluation of a new culture medium for Borrelia burgdorferi - a negative study. Journal of Clinical Microbiology, 2000, 38: 4239-4241.) Continuation of our studies of the immune response to Borrelia burgdorferi. We are currently studying different protocols to increase the specificity of the T cell proliferation assay in Lyme disease, as well as differences in cytokine production. We also continue to investigate the specificity repertoires and function of Borrelia burgdorferi-specific T cell clones that have been isolated from peripheral blood, joint- and/or cerebrospinal fluid from patients with chronic neuroborreliosis and Lyme arthritis (in collaboration with Dr. Roland Martin and Dr. Henry McFarland (Neuroimmunology Branch, NINDS). Studies of MRI patterns in our patients (in collaboration with Dr. Katrin Morgen and Dr. Roland Martin, NINDS). A manuscript has been submitted to the journal Neurology. Studies of neuropsychological profile in patients with chronic Lyme disease (collaboration with Dr. Jordan Grafman, NINDS). Studies of the 8th cranial nerve involvement in chronic Lyme disease (collaboration with Dr. Shotland from NIDCD).